2-Bromo-2',4'-difluoroacetophenone → Hexahydro-2,5-methano-pentalene-3a-carboxylic acid[4-(2,4-difluoro-phenyl)-3-(2-methoxyethyl)-3H-thiazol-2-ylidene]-amide

関与物質

反応手順

To a solution of example 14B (0.21 g, 0.75 mmol) in ethanol (10 mL) was added 2-bromo-1-(2,4-difluorophenyl)ethanone (0.18 g, 0.75 mmol). The mixture was heated to reflux for 3 hours and then concentrated under reduced pressure. The residue was dissolved in ethyl acetate, washed with 1 M aqueous NaHCO3, dried (Na2SO4), filtered and concentrated. Purification by preparative HPLC on a Waters Symmetry C8 column (40 mm×100 mm, 7 μm particle size) using a gradient of 10% to 100% acetonitrile:ammonium acetate (10 mM) over 15 minutes at a flow rate of 70 mL/minutes provided 65 mg (20%) of the title compound. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.47-1.64 (m, 4 H), 1.68-1.84 (m, 4 H), 2.05-2.20 (m, J=11.5 Hz, 2 H), 2.27 (s, 2 H), 2.58 (t, J=6.6 Hz, 1 H), 3.03 (s, 3 H), 3.52 (t, J=5.6 Hz, 2 H), 4.07 (t, J=5.4 Hz, 2 H), 6.99 (s, 1 H), 7.18-7.34 (m, 1 H), 7.48 (td, J=9.7, 2.5 Hz, 1 H), 7.60 (td, J=8.6, 6.6 Hz, 1 H); MS (ESI+) m/z 419 (M+H)+; Anal. Calculated for C22H24F2N2O2S: C, 63.14; H, 5.78; N, 6.69. Found: C, 63.18; H, 5.80; N, 6.72.

情報源と証拠